Citric Acid → 4-Bromo-2-fluoro-5-methylbenzaldehyde

n-BuLi (5.0 ml, 8.0 mmol, 1.6 M in hexane) was added dropwise to a solution of n-Bu2Mg (8.0 ml, 8.0 mmol, 1.0 M in heptane) at room temperature for 10 minutes. The mixture was stirred at room temperature for 15 minutes and then cooled to −10±2° C. A solution of 2,5-dibromo-4-fluorotoluene (5.466 g, 19.59 mmol) in toluene (30 ml)-THF (6 ml) was added dropwise to this mixed reaction solution over 30 minutes, and the mixture was then stirred at 0° C. for one hour. The reaction mixture was added dropwise to a solution cooled to −10° C. of DMF (2.1 ml, 27 mmol) in toluene (7.6 ml) over 15 minutes. Further, this mixture was stirred at −10 to −5° C. for 30 minutes, and then quenched with an aqueous citric acid solution (2.3 M, 16 ml, 37 mmol) and extracted with Et2O. The organic layer was washed with water, and then dried over MgSO4 and concentrated under reduced pressure to give 4-bromo-2-fluoro-5-methyl-benzaldehyde (3.74 g, 88%).

1. temperaturecooled to −10±2° C
2. stirringthe mixture was then stirred at 0° C. for one hour
3. additionThe reaction mixture was added dropwise to a solution
4. stirringFurther, this mixture was stirred at −10 to −5° C. for 30 minutes
5. extractionextracted with Et2O
6. washThe organic layer was washed with water
7. dry with materialdried over MgSO4
8. concentrationconcentrated under reduced pressure

ORD record

ord-87e6316ef6fb45feb0fbb1d1dfd5072b

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169254B2